NNK EFFECTS ON RECEPTOR PATHWAYS IN LUNG CELLS

描述：神经内分泌癌和外周腺癌是最常见的恶性肿瘤。 最常见的肺癌组织类型与吸烟有关。 的 烟碱衍生的亚硝胺，4-（甲基亚硝胺基）-1-（2-吡啶基）-1- 丁酮（NNK）是最丰富和最强的致癌物质之一 含在香烟烟雾中。 NNK诱导高发病率， 实验室啮齿类动物肺中的外周腺癌 在环境空气条件下， 神经内分泌分化时给予高氧仓鼠。 已经证明NNK与烟碱胆碱能和β-肾上腺素能结合， 仓鼠肺和肺癌细胞系中的受体 拟研究NNK对有丝分裂信号转导的影响 由这些受体类型刺激的通路。 具体目标 已经表明NNK诱导的源自于 周围型肺腺癌与β肾上腺素能受体结合 受体（b-AR）和环AMP的激活，Schuller博士将研究 NNK对该信号转导通路的急性和慢性作用 体外使用正常和NNK转化的人支气管细胞， 正常仓鼠Clara细胞以及来源于人的细胞系， 仓鼠肺腺癌作为模型系统。

DESCRIPTION: Neuroendocrine cancer and peripheral adenocarcinoma are the most common histological lung cancer types linked with smoking. The nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(2-pyridyl)-1- butanone (NNK) is among the most abundant and potent carcinogens contained in cigarette smoke. NNK induces a high incidence of peripheral adenocarcinomas in the lungs of laboratory rodents maintained under ambient air conditions while it causes lung cancers of neuroendocrine differentiation when administered to hyperoxic hamsters. Having shown that NNK binds to nicotinic cholinergic and beta-adrenergic receptors in hamster lung and lung cancer cell lines Dr. Schuller proposes to study the effects of NNK on mitogenic signal transduction pathways stimulated by these receptor types. Specific Aim Having shown that NNK-induced mitogenesis of cell lines derived from peripheral pulmonary adenocarcinomas involves binding to beta adrenergic receptors (b-AR) and activation of cyclic AMP, Dr. Schuller will study the acute and chronic effects of NNK on this signal transduction pathway in vitro using normal and NNK transformed human bronchial cells and normal hamster Clara cells as well as cell lines derived from human and hamster lung adenocarcinomas as model systems.